Androgenetic alopecia(AGA)is a common clinical condition,affecting over 200 million people globally each year.For decades,Minoxidil(Mi)tincture has been the primary treatment for this disease,but its low utilization r...Androgenetic alopecia(AGA)is a common clinical condition,affecting over 200 million people globally each year.For decades,Minoxidil(Mi)tincture has been the primary treatment for this disease,but its low utilization rate and significant side effects necessitate new therapeutic strategies.Nitric oxide(NO)is a signaling molecule in various physiological processes,including vasodilation,immune responses,and cell proliferation.Herein,we constructed a hyaluronic acid liposome(HL)complex as a novel transdermal delivery system(HL@Mi/NONOate)for NO and Mi,which displayed promising transdermal and hair-regrowth effects.In-depth mechanistic studies revealed three potential pathways of the synergistic AGA therapy.First,NO promoted capillary dilation and accelerated blood flow,thus achieving efficient penetration of Mi.Due to the structural advantage of liposomes,the residence time of the Mi in the skin was prolonged.Moreover,HL@Mi/NONOate promoted cell proliferation and angiogenesis,and upregulated the expression of regulatory factors involved in follicle stem cell differentiation.In the AGA model,HL@Mi/NONOate down-regulated the expression of inflammatory factors,inhibiting the inflammation of follicle and improving the microenvironment of hair regrowth.Concurrently,HL@Mi/NONOate upregulated the expression of Ki67 and PCNA proteins in follicle tissues,inducing follicle regeneration and development,ultimately achieving the synergistic multimodal AGA therapy.展开更多
基金financially supported by the National Natural Science Foundation of China(32171369 and 82102113)2023 cross-research project on basal research fund in central universities(21623410)+1 种基金the Jinan University-Honest Medical Joint Innovation Center(HX20220013)the Pre-study on transdermal technology and product development(ZX20220244)。
文摘Androgenetic alopecia(AGA)is a common clinical condition,affecting over 200 million people globally each year.For decades,Minoxidil(Mi)tincture has been the primary treatment for this disease,but its low utilization rate and significant side effects necessitate new therapeutic strategies.Nitric oxide(NO)is a signaling molecule in various physiological processes,including vasodilation,immune responses,and cell proliferation.Herein,we constructed a hyaluronic acid liposome(HL)complex as a novel transdermal delivery system(HL@Mi/NONOate)for NO and Mi,which displayed promising transdermal and hair-regrowth effects.In-depth mechanistic studies revealed three potential pathways of the synergistic AGA therapy.First,NO promoted capillary dilation and accelerated blood flow,thus achieving efficient penetration of Mi.Due to the structural advantage of liposomes,the residence time of the Mi in the skin was prolonged.Moreover,HL@Mi/NONOate promoted cell proliferation and angiogenesis,and upregulated the expression of regulatory factors involved in follicle stem cell differentiation.In the AGA model,HL@Mi/NONOate down-regulated the expression of inflammatory factors,inhibiting the inflammation of follicle and improving the microenvironment of hair regrowth.Concurrently,HL@Mi/NONOate upregulated the expression of Ki67 and PCNA proteins in follicle tissues,inducing follicle regeneration and development,ultimately achieving the synergistic multimodal AGA therapy.
